Superoxide electron transport

IV. Superoxide dismutase (EC 1.15.1.1) Within a cell the superoxide dismutases (SODs) constitute the first line of defense against ROS. Superoxide radical (02) is produced where an electron transport chain is present, as in mitochondria and chloroplasts, but 02 activation may occur in other subcellular locations such as glyoxysomes, peroxisomes, apoplast and the cytosol. Thus SODs are present in all these cellular locations, converting superoxide into hydrogen peroxide and water (i.e. copper/zinc SODs are typically found in the nuclei and cytosol of eukaryotic cells). 

FIGURE 32-7 Sources of free radical formation which may contribute to injury during ischemia-reperfusion. Nitric oxide synthase, the mitochondrial electron-transport chain and metabolism of arachidonic acid are among the likely contributors. CaM, calcium/calmodulin FAD, flavin adenine dinucleotide FMN, flavin mononucleotide HtT, tetrahydrobiopterin HETES, hydroxyeicosatetraenoic acids L, lipid alkoxyl radical LOO, lipid peroxyl radical NO, nitric oxide 0 "2, superoxide radical. 

Mitochondrial function. NO is able to react with transition metals such as iron, including those contained within haem groups. Even at low NO concentrations there is competition between oxygen and NO for reversible binding to cytochrome c oxidase. If mitochondrial 02 is low respiration slows, which may confer anti-apoptotic benefit to the cell. As NO concentration rises and peroxynitrite is formed, electron transport is irreversibly inhibited, there is increased production of superoxide and other reactive oxygen species and apoptosis occurs. 

An effect secondary to the activation of enzymes by increased calcium levels can be increased production of reactive oxygen and nitrogen species. Thus, activation of mitochondrial dehydrogenases increases NADH production and electron transport, yet increased calcium uncouples ATP synthesis, and the excess electron generates superoxide. Calcium also activates nitric oxide synthetase. 

The structure of doxorubicin includes a quinone moiety therefore, it can easily accept an electron and undergo redox cycling (Fig. 7.47). Because it accumulates in the mitochondria, it can accept electrons from the electron transport chain and divert them away from complex I. It becomes reduced to the semiquinone radical in the process. This will then reduce oxygen to superoxide and return to the quinone form (Fig. 7.47). This could lead to oxidation of GSH and mtDNA. The subsequent damage may lead to the opening of the mitochondrial permeability transition pore. Consequently, mitochondrial ATP production will be compromised, and ATP levels will decline. 

This may be due to the interference with the mitochondrial electron transport chain. Thus, cadmium binds to complex III at the Q0 site between semi-ubiquinone and heme b566. This stops delivery of electrons to the heme and allows accumulation of semi-ubiquinone, which in turn transfers the electrons to oxygen and produces superoxide. 

Cylinders and barrels. The twisted P sheets of proteins are often curved to form structures known as P cylinders or p barrels (Fig. 2-16).113 114 Simple cylinders formed by parallel P strands form the backbones of the electron transport protein plastocyanin, the enzyme superoxide dismutase, the oxygen carrier... 

Since other membranes have an integral transmembrane electron transport system, the question arises whether these electron carriers can be involved in an oxidation-reduction driven proton movement. In neutrophil as well as macrophage plasma membranes, the answer is already yes. The superoxide-producing NADPH oxidase in these membranes is associated with a channel for proton movement to accompany the electron flow when internal NADPH is oxidized by external oxygen to produce superoxide (Nanda et al., 1993). This is a relatively simple electron transport system which contains a heterodimeric cytochrome b which also binds flavin. Thus, two proteins in a transmembrane electron transport system can transfer protons across the membrane. 

Figure 6. Scheme to represent known aspects of the plasma membrane NADH oxidase and its association with proton release. The oxidase is activated when hormones or ferric transferrin bind receptors. Oxidase may activate tyrosine kinase which can activate MAP kinases to result in phosphorylation of the exchanger leading to Na+/H+ exchange. Oxidation of quinol in the membrane can also release protons to the outside equal to the number of electrons transferred. External ferricyanide can activate electron flow by accepting electrons at the quinone. G proteins (GTP binding proteins) such as ras-activate electron transport and proton release in some way and may be a link to kinase activation (McCormick, 1993). Semiquinone formation in the membrane could lead to superoxide and peroxide formation by one electron reduction of oxygen. 

St-Pierre J, Buckingham JA, Roebuck SJ, Brand MD (2002) Topology of superoxide production from different sites in the mitochondrial electron transport chain. J Biol Chem 277 44784-44790... 

Several metals, for example Cu, Zn, and Mn, are associated with a group of enzymes called superoxide dismutases. These enzymes scavenge the superoxide anion, Oj, which may be a by-product of various redox reactions or the electron transport system (Chapter 17). The superoxide anion gives rise to the very de-... 

---